FI62073C - Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-bensodiazepin-2-on deivat - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-bensodiazepin-2-on deivat Download PDFInfo
- Publication number
- FI62073C FI62073C FI751898A FI751898A FI62073C FI 62073 C FI62073 C FI 62073C FI 751898 A FI751898 A FI 751898A FI 751898 A FI751898 A FI 751898A FI 62073 C FI62073 C FI 62073C
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- phenyl
- tetrahydro
- benzodiazepin
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 8
- ROXAFEIDZVHGFX-UHFFFAOYSA-N 1,3,4,5-tetrahydro-1,4-benzodiazepin-2-one Chemical compound N1C(=O)CNCC2=CC=CC=C21 ROXAFEIDZVHGFX-UHFFFAOYSA-N 0.000 title description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 53
- -1 hydrazinocarbonyl group Chemical group 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000002516 radical scavenger Substances 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- 125000004997 halocarbonyl group Chemical group 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000005059 halophenyl group Chemical group 0.000 claims description 5
- 229940049706 benzodiazepine Drugs 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000006331 halo benzoyl group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 238000007098 aminolysis reaction Methods 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
- 238000002844 melting Methods 0.000 description 50
- 230000008018 melting Effects 0.000 description 50
- 238000001953 recrystallisation Methods 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- 239000007858 starting material Substances 0.000 description 41
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000000203 mixture Substances 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000395 magnesium oxide Substances 0.000 description 6
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 6
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 150000004292 cyclic ethers Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001624 sedative effect Effects 0.000 description 3
- MHQHHBYRYFICDV-UHFFFAOYSA-M sodium;pyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].O=C1CC(=O)[N-]C(=O)N1 MHQHHBYRYFICDV-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- XOIBKUCBAUUKNE-UHFFFAOYSA-N 7-nitro-5-phenyl-1,3,4,5-tetrahydro-1,4-benzodiazepin-2-one Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CNC1C1=CC=CC=C1 XOIBKUCBAUUKNE-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 150000001339 alkali metal compounds Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 229960003529 diazepam Drugs 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 2
- 229960002456 hexobarbital Drugs 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000007530 organic bases Chemical group 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000004627 sleep-enhancing effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- KIUPCUCGVCGPPA-UHFFFAOYSA-N (5-methyl-2-propan-2-ylcyclohexyl) carbonochloridate Chemical compound CC(C)C1CCC(C)CC1OC(Cl)=O KIUPCUCGVCGPPA-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- HRVRAYIYXRVAPR-UHFFFAOYSA-N 1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical class N1C(=O)CCCC2=CC=CC=C21 HRVRAYIYXRVAPR-UHFFFAOYSA-N 0.000 description 1
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
- FMMHUIFSJWVNAE-UHFFFAOYSA-N 1h-1,3-benzodiazepine Chemical class N1C=NC=CC2=CC=CC=C12 FMMHUIFSJWVNAE-UHFFFAOYSA-N 0.000 description 1
- QEYQSYAGLRIYBE-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1,2-benzodiazepine Chemical class C1CCNNC2=CC=CC=C21 QEYQSYAGLRIYBE-UHFFFAOYSA-N 0.000 description 1
- MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical compound N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 description 1
- YYVKQFQZKSLYFN-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-diazepine Chemical class C1CNNC=CC1 YYVKQFQZKSLYFN-UHFFFAOYSA-N 0.000 description 1
- FUNKWXDYVOJNKG-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]azepine Chemical compound N1CCCCC2=CN=CC=C21 FUNKWXDYVOJNKG-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- 125000003541 2-chlorobenzoyl group Chemical group ClC1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- ZYOLWAPZVQXTTM-UHFFFAOYSA-N 7-chloro-1-methyl-5-phenyl-4,5-dihydro-3h-1,4-benzodiazepin-2-one Chemical compound N1CC(=O)N(C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1 ZYOLWAPZVQXTTM-UHFFFAOYSA-N 0.000 description 1
- GYQOYYFIHYKFEO-UHFFFAOYSA-N 7-chloro-5-phenyl-1,3,4,5-tetrahydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)CNC1C1=CC=CC=C1 GYQOYYFIHYKFEO-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- OQXAGCOABDGZHF-UHFFFAOYSA-N C(CCC)OC(=O)N1CC(NC2=C(C1C1=CC=CC=C1)C=C(C=C2)[N+](=O)[O-])=O Chemical compound C(CCC)OC(=O)N1CC(NC2=C(C1C1=CC=CC=C1)C=C(C=C2)[N+](=O)[O-])=O OQXAGCOABDGZHF-UHFFFAOYSA-N 0.000 description 1
- UIFJQOZXJPHHNV-UHFFFAOYSA-N CN1C(CN(C(C2=C1C=CC(=C2)[N+](=O)[O-])C2=CC=CC=C2)C(=O)OC)=O Chemical compound CN1C(CN(C(C2=C1C=CC(=C2)[N+](=O)[O-])C2=CC=CC=C2)C(=O)OC)=O UIFJQOZXJPHHNV-UHFFFAOYSA-N 0.000 description 1
- ZVQOJTSPHSKQLT-UHFFFAOYSA-N COC(=O)N1CC(NC2=C(C1C1=CC=CC=C1)C=C(C=C2)Cl)=O Chemical compound COC(=O)N1CC(NC2=C(C1C1=CC=CC=C1)C=C(C=C2)Cl)=O ZVQOJTSPHSKQLT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical class CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000160765 Erebia ligea Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- PQUGCKBLVKJMNT-UHFFFAOYSA-N SC560 Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(C(F)(F)F)=N1 PQUGCKBLVKJMNT-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910000287 alkaline earth metal oxide Inorganic materials 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical group O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 150000001983 dialkylethers Chemical class 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000005554 hypnotics and sedatives Substances 0.000 description 1
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- YSYGDQNGJARPEF-UHFFFAOYSA-N methyl 7-nitro-2-oxo-5-phenyl-3,5-dihydro-1H-1,4-benzodiazepine-4-carboxylate Chemical compound COC(=O)N1CC(NC2=C(C1C1=CC=CC=C1)C=C(C=C2)[N+](=O)[O-])=O YSYGDQNGJARPEF-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 150000003388 sodium compounds Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI751898A FI62073C (fi) | 1975-06-26 | 1975-06-26 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-bensodiazepin-2-on deivat |
| FI810545A FI67079C (fi) | 1975-06-26 | 1981-02-23 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-benzodiazepin-2-on deivat |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI751898 | 1975-06-26 | ||
| FI751898A FI62073C (fi) | 1975-06-26 | 1975-06-26 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-bensodiazepin-2-on deivat |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI751898A7 FI751898A7 (Direct) | 1976-12-27 |
| FI62073B FI62073B (fi) | 1982-07-30 |
| FI62073C true FI62073C (fi) | 1982-11-10 |
Family
ID=8509299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI751898A FI62073C (fi) | 1975-06-26 | 1975-06-26 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-bensodiazepin-2-on deivat |
Country Status (1)
| Country | Link |
|---|---|
| FI (1) | FI62073C (Direct) |
-
1975
- 1975-06-26 FI FI751898A patent/FI62073C/fi not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI62073B (fi) | 1982-07-30 |
| FI751898A7 (Direct) | 1976-12-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU640113B2 (en) | Benzodiazepine analogs | |
| US5585376A (en) | 1,5-benzodiazepine derivatives having CCK and/or gastrin antagonistic activity | |
| KR900006749B1 (ko) | 항염증성 및 진통성의 활성을 갖는 벤조산 및 벤조산 에스테르의 유도체 | |
| US9242941B2 (en) | Alkyl, fluoroalkyl-1,4-benzodiazepinone compounds | |
| EP0636123A1 (en) | 3-ureido substituted benzodiazepin-2-ones having cholecystokinin and/or gastrin antagonistic activity and their use in therapy | |
| JPH05178843A (ja) | ベンゾジアゼピン誘導体、それらを含有した組成物及びそれらの治療に関する用途 | |
| EP0538945A1 (en) | Benzodiazepine derivatives, and their use as antagonists of gastrin and/or cholecystokinin | |
| AU2013317923A1 (en) | Bis(fluoroalkyl)-1,4-benzodiazepinone compounds as Notch inhibitors | |
| US20150231152A1 (en) | Fluoroalkyl and fluorocycloalkyl 1,4-benzodiazepinone compounds | |
| BG99696A (bg) | Производни на 1,4-бензодиазепин,методи за тяхното получаване, съдържащи ги фармацевтични състави,използването им като сск- модулатори и метод за лечение на състояния,модулирани от сск | |
| EP0280472A1 (en) | Benzodiazepine analogs | |
| AP492A (en) | 1,5 Benzodiazepine derivatives. | |
| DE69409534T2 (de) | Verfahren zur herstellung von benzodiazepin verbindungen verwendbar als cck- oder gastrin-antagonisten | |
| CA2066083C (en) | Benzodiazepine analogs as cholecystokinin antagonists | |
| JPH0680649A (ja) | コレシストキニン拮抗剤 | |
| FI62073C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-ubstituerade 1,3,4,5-tetrahydro-2h-1,4-bensodiazepin-2-on deivat | |
| AU688316B2 (en) | 1,5 benzodiazepine derivatives having CCK and/or gastrin antagonistic activity | |
| AU5099200A (en) | Pharmaceutical compositions comprising iron chelators for the treatment of neurodegenerative disorders and some novel iron chelators | |
| DK153479B (da) | Analogifremgangsmaade til fremstilling af 1,4-benzodiazepin-2-on-derivater | |
| DE69113505T2 (de) | Spiro-Derivate von Dibenzosuberan. | |
| EP2867205A1 (en) | Novel cholecystokinin receptor ligands | |
| US4395409A (en) | Carbamoyloxyamino-1,4-benzodiazepines and medicaments containing these compounds | |
| AU618220B2 (en) | New 2-carbonyl substituted n, n'-di-(trimethoxybenzoyl) piperazines, process for preparing the same and therapeutical compounds containing them | |
| US5206237A (en) | Benzodiazepine analogs | |
| US3882101A (en) | 2-Halo-5-aryl-3H-1,4-benzodiazepines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: RICHTER GEDEON VEGYESZETI GYOER R.T. |